Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway

Dai, Sheng-Nan; Hou, Ai-jie; Zhao, Song; Chen, Xiaoming; Huang, Huating; Chen, Bo-Han; Kong, Hongliang

doi:10.1007/s11655-018-3018-y

Cited by 13 publications

(8 citation statements)

References 44 publications

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“…Inhibitors are widely applied in the investigation of signalling pathways, such as NAC (a ROS scavenger) and SP600125 (a JNK inhibitor) 33,34 . In this study, both NAC and SP600125 suppressed the growth inhibition of HL60 cells induced by compound #2 , indicating the importance of ROS/JNK pathway in the cell viability (Figure 5A).…”

Section: Discussionmentioning

confidence: 55%

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway

Chen

Zhang

et al. 2021

Basic Clin Pharma Tox

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Oleandrigenin‐3‐O‐β‐D‐diginoside (a derivative of odoroside A), isolated and purified by our group, has seldom been explored for its pharmacological activity. This study aimed at clarifying the mechanisms towards the leukaemia‐suppressive role of odoroside A (compound #1) and its derivative, oleandrigenin‐3‐O‐β‐D‐diginoside (compound #2) isolated from Nerium oleander. Viability and nuclear morphology change were assessed by CCK‐8 assay and fluorescence microscope, respectively. Then, the cell apoptosis and autophagy induced by the compounds were detected by flow cytometry and Western blot. Xenograft model of nude mice was also applied to measure the leukaemia‐suppressive effects of compound #2 in vivo. The result displayed that compound #1 and compound #2 inhibited the proliferation of HL60 and K562 cells and stronger effects were found in HL60 than K562 cells. Both of the compounds induced a dose‐dependent apoptosis and autophagy in HL60 cells, where compound #2 was more potent than compound #1. Compound #2 also demonstrated a time‐dependent apoptosis and autophagy in HL60 cells. Furthermore, ROS generation and JNK phosphorylation occurred in a dose‐dependent manner in the cells treated with compound #2. Mitochondria also played critical role, proved by the decrease of Bcl‐2, the release of cyto c to cytosol and the activation of caspase‐3 and caspase‐9. Moreover, the antitumour effects of compound #2 were validated in the nude mouse xenograft model in vivo. Odoroside A and its derivative inhibited the growth of leukaemia by inducing apoptosis and autophagy through the activation of ROS/JNK pathway. These results suggest that the compounds can serve as potential antitumour agents against leukaemia, especially acute myeloid leukaemia (AML).

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Section: Discussionmentioning

confidence: 55%

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway

Chen

Zhang

et al. 2021

Basic Clin Pharma Tox

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“…Notably, Rb1 was reported to have pleiotropic cardiovascular protection effects on multiple molecular targets independently, mainly including AMPK, PI3K/Akt, NF-κB, and mitogen-activated protein kinase (MAPK) pathways and endoplasmic reticulum stress. AMPK participates in the cardiovascular protection effect of Rb1 against reperfusion injury/myocardial ischemia, coronary atherosclerotic, heart failure, cardiac hypertrophy, and fibrosis by mediating apoptosis (Kong et al, 2010), autophagy (Qiao et al, 2017;Dai et al, 2019), mitochondrial fission (Li et al, 2016), fatty acid β-oxidation (Kong et al, 2018), and aging (Zheng et al, 2020). In the meantime, the changes in Akt signaling are of importance in atherosclerosis, cardiac hypertrophy, vascular remodeling, and many other cardiovascular pathological processes.…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rb1 Ameliorates Diabetic Arterial Stiffening via AMPK Pathway

Zhang

Wang

Guo³

et al. 2021

Front. Pharmacol.

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Background and Purpose: Macrovascular complication of diabetes mellitus, characterized by increased aortic stiffness, is a major cause leading to many adverse clinical outcomes. It has been reported that ginsenoside Rb1 (Rb1) can improve glucose tolerance, enhance insulin activity, and restore the impaired endothelial functions in animal models. The aim of this study was to explore whether Rb1 could alleviate the pathophysiological process of arterial stiffening in diabetes and its potential mechanisms.Experimental Approach: Diabetes was induced in male C57BL/6 mice by administration of streptozotocin. These mice were randomly selected for treatment with Rb1 (10−60 mg/kg, i. p.) once daily for 8 weeks. Aortic stiffness was assessed using ultrasound and measurement of blood pressure and relaxant responses in the aortic rings. Mechanisms of Rb1 treatment were studied in MOVAS-1 VSMCs cultured in a high-glucose medium.Key Results: Rb1 improved DM-induced arterial stiffening and the impaired aortic compliance and endothelium-dependent vasodilation. Rb1 ameliorated DM-induced aortic remodeling characterized by collagen deposition and elastic fibers disorder. MMP2, MMP9, and TGFβ1/Smad2/3 pathways were involved in this process. In addition, Rb1-mediated improvement of arterial stiffness was partly achieved via inhibiting oxidative stress in DM mice, involving regulating NADPH oxidase. Finally, Rb1 could blunt the inhibition effects of DM on AMPK phosphorylation.Conclusion and Implications: Rb1 may represent a novel prevention strategy to alleviate collagen deposition and degradation to prevent diabetic macroangiopathy and diabetes-related complications.

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“…The cup-shaped pre-autophagosomal double-membrane structure containing cytoplasmic material characterizes the formation of autophagosomes (16). As previously reported, the cardiomyocyte-specific abrogation of basal autophagy that results from a deficiency in autophagy protein 5 (Atg5) leads to spontaneous cardiac hypertrophy (17). Accordingly, autophagy acts as a protective mechanism that improves cardiomyocyte survival under stress (18).…”

Section: Introductionmentioning

confidence: 89%

p27kip1 haploinsufficiency preserves myocardial function in the early stages of myocardial infarction via Atg5‑mediated autophagy flux restoration

et al. 2019

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Myocardial infarction (MI) is a leading cause of mortality in adults worldwide. Over the last two decades, gene therapy has been a hot topic in cardiology, and there has been a focus on cell cycle inhibitors and their protective effects on the myocardium post-MI. In our previous study, the haploinsufficiency of p27kip1 (p27) was demonstrated to improve cardiac function in mice post-MI by promoting angiogenesis and myocardium protection through the secretion of growth factors. Autophagy is an adaptive response of cells to environmental changes, such as nutrient deprivation, ischemia and hypoxia. The appropriate regulation of autophagy may improve myocardial function by preventing apoptosis of cardiomyocytes. In this study, we used immunoassays, transmission electron microscopy and cardiac ultrasound to confirm that p27 haploinsufficiency prevents myocardial apoptosis by restoring autophagy protein 5-mediated autophagy flux in the early stages of MI. The present study provides a novel method for studying MI or ischemic heart disease therapy.

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Ginsenoside Rb1 Ameliorates Autophagy of Hypoxia Cardiomyocytes from Neonatal Rats via AMP-Activated Protein Kinase Pathway

Abstract: Gs-Rb1 may improve the viability of hypoxia cardiomyocytes by ameliorating cell autophagy via the upregulation of AMPK pathway.

Cited by 13 publications

References 44 publications

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway

Antitumour effect of odoroside A and its derivative on human leukaemia cells through the ROS/JNK pathway

Ginsenoside Rb1 Ameliorates Diabetic Arterial Stiffening via AMPK Pathway

p27kip1 haploinsufficiency preserves myocardial function in the early stages of myocardial infarction via Atg5‑mediated autophagy flux restoration

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